FOXM1 overexpression is associated with adverse outcome and predicts response to intravesical instillation therapy in stage pT1 non-muscle-invasive bladder cancer

Breyer J, Wirtz RM, Erben P, Rinaldetti S, Worst TS, Stoehr R, Eckstein M, Sikic D, Denzinger S, Burger M, Hartmann A, Otto W (2019)


Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 123

Pages Range: 187-196

Journal Issue: 1

DOI: 10.1111/bju.14525

Abstract

OBJECTIVE: To investigate the role of forkhead box protein M1 (FOXM1) mRNA expression and its prognostic value in stage pT1 non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Clinical data and formalin-fixed paraffin-embedded tissues from transurethral resection of the bladder from patients with stage pT1 NMIBC, treated with an organ-preserving approach, were analysed retrospectively. Total RNA was isolated using commercial RNA extraction kits, and mRNA expression of FOXM1, MKI67, KRT20 and KRT5 was measured by single-step quantitative RT-PCR using RNA-specific TaqMan Assays. Statistical analysis was performed using Spearman's Rho, Wilcoxon or Kruskal-Wallis tests, Kaplan-Meier estimates of recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS) and Cox regression analysis. RESULTS: Data from 296 patients (79.4% men, median age 72 years) were available for the final evaluation. Spearman correlation analysis showed that mRNA expression of FOXM1 was significantly correlated with MKI67 (ρ: 0.6530, P < 0.001) and with the luminal subtype, reflected by the positive correlation with KRT20 (ρ: 0.2113, P < 0.001). Furthermore, there was also a strong correlation of FOXM1 expression with adverse clinical and pathological variables, such as concomitant carcinoma in situ (P = 0.05), multifocal tumours (P = 0.005) and World Health Organization 1973 grade 3 disease (P < 0.001). Kaplan-Meier analysis showed overexpression of FOMX1 to be associated with worse PFS (P = 0.028) and worse CSS (P = 0.015). FOXM1 overexpression was also shown to be a predictive risk factor for CSS (hazard ratio 1.61 [1.13-2.34], L-R chi-squared: 7.19, P = 0.007). FOXM1 overexpression identified a subgroup of patients within the luminal subtype with worse RFS (P = 0.017), PFS (P < 0.001) and CSS (P = 0.015). Patients with low FOXM1 expression had better outcomes, irrespective of instillation therapy, whereas patients with high FOXM1 expression benefitted from intravesical chemotherapy with mitomycin C. CONCLUSION: High FOXM1 expression was associated with adverse clinical and pathological features and worse outcomes, and predicted response to intravesical instillation therapy in patients with stage pT1 NMIBC.

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APA:

Breyer, J., Wirtz, R.M., Erben, P., Rinaldetti, S., Worst, T.S., Stoehr, R.,... Otto, W. (2019). FOXM1 overexpression is associated with adverse outcome and predicts response to intravesical instillation therapy in stage pT1 non-muscle-invasive bladder cancer. Bju International, 123(1), 187-196. https://dx.doi.org/10.1111/bju.14525

MLA:

Breyer, Johannes, et al. "FOXM1 overexpression is associated with adverse outcome and predicts response to intravesical instillation therapy in stage pT1 non-muscle-invasive bladder cancer." Bju International 123.1 (2019): 187-196.

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